"We have to find a way to mass-produce them because traditional
cell culturing methods can't meet the projected high market demand for
stem cells," Yang said.

He and Anli Ouyang, a doctoral student in chemical engineering, grew
mouse embryonic stem cells in a bioreactor. Cell growth increased 193-fold
in 15 days. At the end of that period, cell density – the number
of cells that had grown in the bioreactor – was anywhere from 10-
to 100-fold higher than the number of stem cells produced by conventional
laboratory methods. That's several hundreds of millions more stem cells.

Mass-producing cells like this could reduce stem cell production costs
by at least 80 percent, Yang said, as it requires less equipment and monitoring.

"We have to find
a way to mass-produce stem cells because traditional cell culturing
methods can't meet the projected high market demand for stem cells,"
Yang said.

Embryonic stem cells are unspecialized, or undifferentiated, cells that
can grow into any of the body's 200 different types of cells.

They grew some mouse embryonic stem cells in a flask – a conventional
way to grow stem cells – while other stem cells grew upon strands
of polymer threads inside a bioreactor.

The bioreactor used in this study is a tissue-growing device developed
by Ohio State scientists. While this bioreactor could be used to produce
adult stem cells, the researchers chose to look solely at embryonic stem
cells for this experiment.

"There's more of a demand for an unlimited supply of embryonic
stem cells," Yang said. Also, embryonic stem cells are pluripotent
– they can become any kind of cell in the body, while adult stem
cells usually develop into a type of cell based on the kind of tissue
that they originated from.

The bioreactor has a chamber that holds the polymer threads on which
the stem cells grow and another chamber that holds fluid, or medium. This
medium delivers chemical messengers, called cytokines, to the stem cells.
The cytokines essentially tell the stem cells to stay in their undifferentiated
state.

The difference between growing stem cells in a flask vs. the bioreactor
is that the cells grown in the bioreactor could grow in three dimensions,
while cells growing on a flat surface – the bottom of the flask
– could not.

“Cells grown on a flat surface don't act like they would in the
body," Yang said. "The growing surface affects how a cell forms,
what it looks like and even how it expresses genes."

Cells grown in the bioreactor could grow for a much longer period of
time than they could in the flask, as cells had more room to grow in the
bioreactor.

"In the same amount of time we could grow up to a billion stem
cells per milliliter in the bioreactor, compared to tens of millions of
cells per milliliter with conventional systems," Yang said.

Also, it seems that embryonic stem cells grown by conventional methods
are more likely to spontaneously differentiate, or change. Researchers
aren't sure why or how some stem cells differentiate without prompting.

Yang and Ouyang tested both sets of cells – the ones grown in
a flask and those grown in the bioreactor – for two key proteins.
The presence of these proteins indicates that a stem cell has not differentiated.
In the bioreactor experiment, 94 percent of the stem cells tested positive
for these proteins, compared to about 85 percent of the cells grown in
the flask.

The researchers are now working on ways to program embryonic stem cells
so that they differentiate into specific types of cells. In preliminary
work, Ouyang has created a network of neurons from undifferentiated embryonic
stem cells.

The next step is to use human embryonic stem cells, and the researchers
have yet to decide which line of stem cells to use.

The mouse embryonic stem cells used in this study were provided by ATCC,
an organization that supplies lines of embryonic stem cell lines.